IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa
IL-23-mediated regulation of IL-17 production in Helicobacter pylori-infected gastric mucosa
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DOI：
10.1002/eji.200737635
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发表时间：
2008-02-01
影响因子：
5.4
通讯作者：
Monteleone, Giovanni
中科院分区：
文献类型：
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作者：
Caruso, Roberta;Fina, Daniele;Monteleone, Giovanni
幽门螺杆菌（Hp）感染与炎症细胞在胃黏膜的显著浸润有关。控制幽门螺杆菌相关炎症反应的分子途径是复杂的，但局部诱导产生的细胞因子似乎有助于维持持续的炎症。我们先前已经表明，白细胞介素 - 17在幽门螺杆菌感染的胃黏膜中过度产生，并且白细胞介素 - 17刺激白细胞介素 - 8（主要的中性粒细胞趋化因子）的合成。然而，调节白细胞介素 - 17表达的因素/机制仍然未知。在这项研究中，我们首先扩展了我们先前的数据，表明CD4(+)和CD8(+) T细胞是幽门螺杆菌感染样本中白细胞介素 - 17的一个来源。由于在细菌感染期间白细胞介素 - 23增强T细胞衍生的白细胞介素 - 17，我们随后评估了白细胞介素 - 23在控制幽门螺杆菌定植的胃中白细胞介素 - 17表达的作用。通过实时定量聚合酶链反应和酶联免疫吸附测定，在所有胃活检组织中都检测到了白细胞介素 - 23，但与对照组相比，其在幽门螺杆菌感染的样本中表达更为显著。用白细胞介素 - 23处理正常胃固有层单核细胞（LPMC）增强了Stat3的活化和白细胞介素 - 17的分泌，并且对Stat3的药理抑制阻止了白细胞介素 - 23驱动的白细胞介素 - 17合成。同样，在来自幽门螺杆菌感染患者的LPMC培养物中阻断白细胞介素 - 23降低了Stat3的活化和白细胞介素 - 17的产生。数据表明，白细胞介素 - 23在幽门螺杆菌感染的胃黏膜中过度表达，它可能有助于维持白细胞介素 - 17的产生。
Helicobacter pylori (Hp) infection is associated with a marked infiltration of the gastric mucosa by inflammatory cells. The molecular pathways that control Hp-associated inflammatory reaction are complex, but locally induced cytokines seem to contribute to maintaining the ongoing inflammation. We have previously shown that IL-17 is overproduced in Hp-infected gastric mucosa, and that IL-17 stimulates the synthesis of IL-8, the major neutrophil chemoattractant. Factors/mechanisms that regulate IL-17 expression remain, however, unknown. In this study, we initially expanded our previous data, showing that CD4(+) and CD8(+) T cells are a source of IL-17 in Hp-infected samples. Since IL-23 enhances T cell-derived IL- 17 during bacterial infections, we then assessed the role of IL-23 in controlling IL-17 expression in Hp-colonized stomach. Using real-time PCR and ELISA, IL-23 was detected in all gastric biopsies, but its expression was more pronounced in Hp-infected samples in comparison to controls. Treatment of normal gastric lamina propria mononuclear cells (LPMC) with IL-23 enhanced Stat3 activation and IL-17 secretion, and pharmacological inhibition of Stat3 prevented IL-23-driven IL-17 synthesis. Consistently, blockade of IL-23 in cultures of LPMC from Hp-infected patients reduced Stat3 activation and IL-17 production. Data show that IL-23 is overexpressed in Hp-infected gastric mucosa where it could contribute to sustaining IL-17 production.